TY - JOUR
T1 - Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
AU - Elbaz, Alexis
AU - Ross, Owen A.
AU - Ioannidis, John P.A.
AU - Soto-Ortolaza, Alexandra I.
AU - Moisan, Frédéric
AU - Aasly, Jan
AU - Annesi, Grazia
AU - Bozi, Maria
AU - Brighina, Laura
AU - Chartier-Harlin, Marie Christine
AU - Destée, Alain
AU - Ferrarese, Carlo
AU - Ferraris, Alessandro
AU - Gibson, J. Mark
AU - Gispert, Suzana
AU - Hadjigeorgiou, Georgios M.
AU - Jasinska-Myga, Barbara
AU - Klein, Christine
AU - Krüger, Rejko
AU - Lambert, Jean Charles
AU - Lohmann, Katja
AU - Van De Loo, Simone
AU - Loriot, Marie Anne
AU - Lynch, Timothy
AU - Mellick, George D.
AU - Mutez, Eugénie
AU - Nilsson, Christer
AU - Opala, Grzegorz
AU - Puschmann, Andreas
AU - Quattrone, Aldo
AU - Sharma, Manu
AU - Silburn, Peter A.
AU - Stefanis, Leonidas
AU - Uitti, Ryan J.
AU - Valente, Enza Maria
AU - Vilariño-Güell, Carles
AU - Wirdefeldt, Karin
AU - Wszolek, Zbigniew K.
AU - Xiromerisiou, Georgia
AU - Maraganore, Demetrius M.
AU - Farrer, Matthew J.
PY - 2011/5
Y1 - 2011/5
N2 - Objective: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. Methods: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. Results: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects.
AB - Objective: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. Methods: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. Results: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects.
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U2 - 10.1002/ana.22321
DO - 10.1002/ana.22321
M3 - Article
C2 - 21391235
AN - SCOPUS:79955389000
SN - 0364-5134
VL - 69
SP - 778
EP - 792
JO - Annals of neurology
JF - Annals of neurology
IS - 5
ER -